Hypercortisolism:

A. Is most often ACTH-dependent, owing to an ACTH-producing pituitary adenoma.

D. May be caused by small cell carcinoma of the lung, carcinoid tumors, tumors of the endocrine pancreas, pheochromocytoma, or medullary thyroid carcinoma (MTC).

E. In children is most often caused by adrenocortical neoplasia.

DISCUSSION: Cushing's syndrome is most often (80% to 90%) ACTH-dependent and is most often due to an ACTHsecreting pituitary adenoma (Cushing's disease). Some 10% to 20% of ACTH-dependent Cushing's syndrome is caused by ectopic production of ACTH from small cell carcinoma of the lung, carcinoid tumors, tumors of the endocrine pancreas, pheochromocytoma, and MTC. ACTH-independent Cushing's syndrome secondary to primary adrenal pathology occurs in 10% to 20% of cases in adults and is the most common form in children. Measurement of cortisol in two to three consecutive 24-hour collections of urine is the best screening test for Cushing's syndrome: plasma levels of cortisol show marked variability, and a single random level is not helpful in establishing the diagnosis. ACTH-independent Cushing's syndrome suppresses the pituitary and is diagnosed if the basal serum ACTH level is suppressed below 5 pg. per ml., if the hypercortisolism is not suppressed by high-dose dexamethasone, or if the metyrapone stimulation test is negative. The dexamethasone suppression and metyrapone tests do not, however, distinguish an adrenal from an ectopic ACTH cause of Cushing's since both suppress the pituitary. Radiographic evidence of an adrenal tumor must be supported by biochemical testing to confirm that the adrenal is the primary cause of Cushing's syndrome